Parasitic infection is treated, or prevented, by the administration of a drug or drugs, such as xenobiotic chemotherapeutic drugs, to a susceptible or infected host organism. Effective treatment of parasitic infection by drug administration is frequently impaired, however, due to resistance of the parasite to the drug. Such resistance can be “inherent” to the parasite in the sense that the susceptibility of the parasite to the drug has not increased due to widespread use of the drug. Commonly, however, drug resistance of infectious parasites is observed due to evolved resistance associated with widespread treatment with the drug and associated selection pressure for resistant phenotypes. Currently, many infectious parasites are completely or highly resistant to available drugs and drug combinations, and parasites still susceptible to available drugs require treatment with greater doses than previously required, such that complete or effectively complete resistance is foreseeable.
For example, chloroquine resistance in certain species of malaria-causing Plasmodium parasites is so widespread that alternative or combination anti-malarial therapies are now required, and many parasitic species, including malaria-causing Plasmodium species, are now multi-drug resistant. As a further example, the incidence of parasite resistance to avermectins, a widely used class of nematicides, acaridices and insecticides in veterinary and human medicine and plant protection, is increasing.
Resistance of infectious parasites to anti-parasitic drugs can be avoided or lessened by rendering the parasites more sensitive to one or more drugs. The calcium channel blocker Verapramil, for example, has been evaluated for its effect on sensitization of parasites to xenobiotics. However, safe, economical, and effective methods for sensitizing parasites in such a manner are lacking.